Synopsis
Recognise calcium-related neurological, renal and cardiac toxicity, restore safe volume, suppress tumour-driven calcium release, identify the biological mechanism and prevent recurrent metabolic deterioration.
- Malignant hypercalcaemia commonly results from PTHrP secretion, osteolytic metastases or myeloma, and less often calcitriol-producing lymphoma; mechanisms may overlap.
- Symptoms include thirst, polyuria, dehydration, constipation, nausea, weakness, cognitive change and shortened-QT or rhythm disturbance; severity depends on rate of rise as well as the number.
- First-line confirmation is repeat albumin-adjusted calcium, or ionised calcium when protein binding is unreliable, with renal function, phosphate, magnesium and ECG in severe disease.
- Measure intact PTH early: malignant hypercalcaemia usually suppresses it, while a non-suppressed result requires a PTH-dependent branch even in known cancer.
- First-line acute treatment is carefully reassessed intravenous 0.9% sodium chloride to correct volume depletion; routine loop diuresis is not calcium treatment and is reserved for genuine overload.
- After hydration and renal assessment, intravenous zoledronic acid 4 mg over at least 15 minutes is a licensed adult option for tumour-induced hypercalcaemia at an adjusted calcium of at least 3.0 mmol/L.
- Antiresorptive effect develops over days, so do not repeat the dose prematurely; severe refractory disease may need calcitonin, denosumab or dialysis through specialist guidance.
- Treat the underlying cancer and create a recurrence plan that includes calcium, renal and companion electrolyte monitoring, hydration access and goals of care.
Key red flags
Confusion, reduced consciousness, seizure or profound weakness with raised calcium indicates neurological toxicity and needs monitored treatment.
Oliguria, rapidly increasing creatinine or inability to tolerate fluid safely requires urgent renal and critical-care input.
Arrhythmia, syncope or a markedly shortened QT with companion potassium or magnesium disturbance increases immediate cardiac risk.
Focal bone pain, inability to weight bear or new spinal neurological features may indicate pathological fracture or MSCC requiring a parallel emergency pathway.
Known cancer must not suppress a second diagnosis: non-suppressed PTH suggests coincident primary hyperparathyroidism or another PTH-dependent cause.
Lethargy, proximal weakness, confusion, agitation, reduced consciousness or seizure reflects important neurological effect and may progress rapidly.
Shortened QT, bradyarrhythmia, conduction change or syncope is concerning, particularly with digoxin exposure or potassium and magnesium disturbance.
Investigation priorities
Confirm true elevation, assess trajectory and avoid protein-binding artefact.
Management branches
Confirmed hypercalcaemia causes symptoms, dehydration, renal injury or cardiac concern.
- Use ABCDE assessment, ECG, neurological examination and accurate fluid balance; repeat calcium and companion electrolytes and stop avoidable calcium-raising medicines and supplements.
- Give intravenous 0.9% sodium chloride in reassessed stages, adapting each prescription to pressure, urine, sodium, lungs, age and cardiac or renal reserve.
- Escalate shock, severe neurological change, arrhythmia, oliguria or inability to hydrate safely to acute oncology, endocrine, renal and critical-care teams.